CN103130684A - Polymorphism of methocarbamol dipotassium phosphate and preparation method thereof - Google Patents
Polymorphism of methocarbamol dipotassium phosphate and preparation method thereof Download PDFInfo
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- CN103130684A CN103130684A CN2013100950423A CN201310095042A CN103130684A CN 103130684 A CN103130684 A CN 103130684A CN 2013100950423 A CN2013100950423 A CN 2013100950423A CN 201310095042 A CN201310095042 A CN 201310095042A CN 103130684 A CN103130684 A CN 103130684A
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Abstract
The invention provides a polymorphism of methocarbamol dipotassium phosphate and a preparation method thereof, and relates to a polymorphism corresponding to 3-(o-methoxyphenoxy)-2-hydroxypropyl amino-acid ester dipotassium phosphate (methocarbamol dipotassium phosphate) and a preparation method thereof. A medicament containing the crystal form can be used for treating muscle sprain, lumbar muscle strain and ischialgia. The crystal form is specified by characterization results of an X-ray powder diffraction pattern (shown as Figure 1), nuclear magnetic resonance absorption spectra (shown as Figures 2-4), a thermogravimetry-differential thermal analysis curve (shown as Figure 5), an infrared spectrum absorption curve (shown as Figure 8) and liquid chromatography/mass spectrometry. The powder of the polymorphism is fine and uniform in dispersion; the stability is increased; the water solubility is 1:1; and the crystallization process is simple and convenient to implement production/transportation/storage, and conforms to the requirements for medicament preparation.
Description
Technical field
The present invention relates to 3-(o-methoxyphenyl)-2-hydroxypropyl amino acid ester di(2-ethylhexyl)phosphate sylvite (methocarbamol di(2-ethylhexyl)phosphate sylvite), and its a kind of polymorphic form and preparation method thereof, contain this crystal formation medicine and can be applicable to treat muscle sprain, lumbar muscle strain, sciatica.
Background technology
In Chinese patent CN101863917A(publication No.) in to have put down in writing 3-(o-methoxyphenyl)-2-hydroxypropyl amino acid ester (methocarbamol) be a kind of active drug for the treatment of muscle epitonos, spasm, the symptom such as tetanic, treatment such as muscle sprain, lumbar muscle strain, sciatica, prolapse of lumbar intervertebral disc in obvious effective rate very high.But because methocarbamol itself is insoluble in water, water-soluble is only 1:210, has been subject to the corresponding detrimentally affect that causes in clinical middle application.
Patent CN101863917A provides methocarbamol has been carried out the synthetic phosphatic method of methocarbamol of structural modification, although improved solubleness, but due to methocarbamol Rhodiaphos DKP salt pair temperature and insensitive, the more difficult solid of separating out after cooling during conventional making with extra care, the solid of separating out is also unstable, and easily the moisture absorption is formed grit.At present not yet relevant for the stable polymorphic report of methocarbamol di(2-ethylhexyl)phosphate sylvite.
Summary of the invention
The objective of the invention is to overcome the prior art above shortcomings, polymorphic of a kind of methocarbamol di(2-ethylhexyl)phosphate sylvite and its preparation method and application is provided.
The polymorphic of methocarbamol di(2-ethylhexyl)phosphate sylvite provided by the invention is referred to as crystal form P, and the fusing point of crystal form P is: 155-158 ℃; The X-ray powder diffraction collection of illustrative plates of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak:
The proton nmr spectra of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak,
1HNMR (400MHz, D
2O): δ=3.75 (s, 3H), 4.08-4.24 (m, 4H), 4.38-4.48 (m, 1H), 6.87-7.08 (m, 4H); Carbon-13 nmr spectra has following peak,
13CNMR (400MHz, D2O): δ=55.68,64.44,68.11,69.65,112.44,113.89,121.57,121.96,147.43,148.40,159.25; Nucleus magnetic resonance phosphorus spectrum has following peak,
31PNMR (400MHz, D
2O): δ=0.47.
The mass spectrometry results of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is ,+c ESI:m/z=398 (M+1), m/z=436 (M+39);-c ESI:m/z=320,641.
The absorption peak wave number corresponding to infrared spectra of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is with cm
-1Expression is respectively: 422.1,440.6,478.1,519.0,535.5,551.8,580.1,614.7,683.4,738.6,757.4,836.3,885.1,906.8,977.7,1024.9,1056.5,1078.1,1114.9,1142.7,1226.1,1255.4,1350.0,1367.3,1381.0,1410.7,1453.7,1508.3,1595.4,1719.8,2044.8,2169.5,2583.8,2835.1,2957.1,3203.6.
Thermogravimetric differential thermal (TG-DTG) analytic curve of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak: 179.2 ℃, and 262.8 ℃; The corresponding weightlessness of TG curve is 14.36%, 37.90%.
The present invention provides polymorphous preparation method of methocarbamol di(2-ethylhexyl)phosphate sylvite simultaneously, the method is in methocarbamol di(2-ethylhexyl)phosphate sylvite is water-soluble or mixed solvent, be heated to be chilled to normal temperature after dissolving fully more than 50 ℃, add poor solvent that crystal is separated out, filter rear 50 ℃ of dry 8h and obtain crystal form P.
Mixed solvent described in the present invention all refers to if no special instructions: the mixed solvent of a kind of composition in water and alcohol, ketone, ether, acid amides or sulfoxide type solvent, the mixed solvent of a kind of composition in water and methyl alcohol, ethanol, Virahol, acetonitrile, acetone, DMF, tetrahydrofuran (THF) or methyl-sulphoxide specifically.
Described poor solvent all refers to if no special instructions: alcohol, ketone, ether, acid amides or sulfoxide type solvent, specifically a kind of in methyl alcohol, ethanol, Virahol, acetonitrile, acetone, DMF, tetrahydrofuran (THF) or methyl-sulphoxide.
The polymorphic of methocarbamol di(2-ethylhexyl)phosphate sylvite provided by the invention can be used for preparing the medicine for the treatment of muscle sprain, lumbar muscle strain or sciatica.
Advantage of the present invention and beneficial effect:
The present invention utilizes intermediate methocarbamol dihydrogen phosphate to synthesize methocarbamol di(2-ethylhexyl)phosphate sylvite, and its polymorphic is studied.Polymorphic by preparation methocarbamol di(2-ethylhexyl)phosphate sylvite after the dissolving of use appropriate solvent, poor solvent crystallization, filtration drying, obtained a kind of stable crystal form P, powder is thin and be uniformly dispersed, stability improves, it is water-soluble is 1:1, this crystallization technique is simple, is convenient to production and transport and stores, and meets the requirement of medicine preparation.
Description of drawings
Fig. 1 is the X-ray powder diffraction collection of illustrative plates of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P;
Fig. 2 is the proton nmr spectra of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P;
Fig. 3 is the carbon-13 nmr spectra of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P;
Fig. 4 is the nucleus magnetic resonance phosphorus spectrum of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P;
Fig. 5 is the thermogravimetric differential thermal analysis curve of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P;
Fig. 6 is that the mass spectrum positive ion of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P goes out peak figure;
Fig. 7 is that the mass spectrum negative ion of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P goes out peak figure;
Fig. 8 is the infrared absorpting light spectra of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P.
Embodiment
The preparation of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P
3.52g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in 3mL distilled water, and heating in water bath to 60 a ℃ solid dissolves fully, is chilled to normal temperature and drips dehydrated alcohol, and crystallization is rear the filtration fully, and 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 155-157 ℃.
13.27g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in 15mL distilled water, and heating in water bath to 55 a ℃ solid dissolves fully, is chilled to normal temperature and drips methyl alcohol, and crystallization is rear the filtration fully, and 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 155-156 ℃.
7.32g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in 10mL distilled water, and heating in water bath to 60 a ℃ solid dissolves fully, is chilled to normal temperature and drips Virahol, and crystallization is rear the filtration fully, and 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 156-157 ℃.
2.65g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in 3mL distilled water, and heating in water bath to 60 a ℃ solid dissolves fully, is chilled to normal temperature and drips acetone, and crystallization is rear the filtration fully, and 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 155-157 ℃.
1.40g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixed solvent of 1.3mL ethanol and 1.3mL distilled water, heating in water bath to 65 a ℃ solid dissolves fully, is chilled to normal temperature and drips dehydrated alcohol, and crystallization is rear the filtration fully, 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 156-158 ℃.
7.21g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in 85% ethanol of 30mL, be heated to boil, backflow 30min treats the solution clarification, stopped heating is standing to be chilled to room temperature and dropwise to add dehydrated alcohol, change 5 ℃ of refrigerator insulation 3h over to after having crystal to separate out, after filtering, 50 ℃ of oven dry 8h of filter cake obtain crystal form P, fusing point 155-158 ℃.
25.31g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixing solutions of 15mL distilled water and 80mL ethanol, be heated to boil, backflow 45min treats the solution clarification, stopped heating is standing to be chilled to room temperature and dropwise to add dehydrated alcohol, change 5 ℃ of refrigerator insulation 2h over to after having crystal to separate out, after filtering, 50 ℃ of oven dry 8h of filter cake obtain crystal form P, fusing point 156-158 ℃.
9.75g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixing solutions of 10mL water and 10mL methyl alcohol, and heating in water bath to 50 a ℃ solid dissolves fully, is chilled to normal temperature and drips methyl alcohol, and crystallization is rear the filtration fully, and 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 155-157 ℃.
9.03g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixing solutions of 10mL water and 10mL Virahol, heating in water bath to 65 a ℃ solid dissolves fully, is chilled to normal temperature and drips Virahol, and crystallization is rear the filtration fully, 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 156-157 ℃.
13.88g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixed solvent of 15mL acetone and 15mL distilled water, heating in water bath to 55 a ℃ solid dissolves fully, is chilled to normal temperature and drips acetone, and crystallization is rear the filtration fully, 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 156-158 ℃.
Embodiment 11
5.99g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixed solvent of 7.5mL ethanol and 7.5mL distilled water, heating in water bath to 65 a ℃ solid dissolves fully, is chilled to normal temperature and drips acetone, and crystallization is rear the filtration fully, 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 156-157 ℃.
Embodiment 12
4.87g methocarbamol di(2-ethylhexyl)phosphate sylvite is dissolved in the mixed solvent of 10mL ethanol and 7.5mL distilled water, heating in water bath to 70 a ℃ solid dissolves fully, is chilled to normal temperature and drips dehydrated alcohol, and crystallization is rear the filtration fully, 50 ℃ of oven dry 8h obtain crystal form P, and fusing point is: 155-157 ℃.
The polymorphous parametric measurement of methocarbamol di(2-ethylhexyl)phosphate sylvite
1, the X-ray powder diffraction collection of illustrative plates (as shown in Figure 1) of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak:
The test condition of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P being carried out the X-ray powder diffraction sign is:
2, the proton nmr spectra (as shown in Figure 2) of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak,
1HNMR (400MHz, D
2O): δ=3.75 (s, 3H), 4.08-4.24 (m, 4H), 4.38-4.48 (m, 1H), 6.87-7.08 (m, 4H); Carbon-13 nmr spectra (as shown in Figure 3) has following peak,
13CNMR (400MHz, D
2O): δ=55.68,64.44,68.11,69.65,112.44,113.89,121.57,121.96,147.43,148.40,159.25; Nucleus magnetic resonance phosphorus spectrum (as shown in Figure 4) has following peak,
31PNMR (400MHz, D
2O): δ=0.47.
The condition of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P being carried out the nucleus magnetic resonance test is:
Instrument: the Bruker400M nmr spectrometer,
Solvent: D
2O，
Content:
1HNMR,
13CNMR,
31PNMR.
3, mass spectrum (as shown in Figure 6 and Figure 7) analytical results of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is ,+c ESI:m/z=398 (M+1), m/z=436 (M+39);-c ESI:m/z=320,641.
Methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is carried out the mass spectroscopy condition is:
Instrument: Thermo Fisher Finnigan LCQ Advantage,
Method: LC-MS,
Ion source: ESI,
Mass charge ratio range: 50-2000.
4, absorption peak wave number corresponding to the infrared spectra (as shown in Figure 8) of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is with cm
-1Expression is respectively: 422.1,440.6,478.1,519.0,535.5,551.8,580.1,614.7,683.4,738.6,757.4,836.3,885.1,906.8,977.7,1024.9,1056.5,1078.1,1114.9,1142.7,1226.1,1255.4,1350.0,1367.3,1381.0,1410.7,1453.7,1508.3,1595.4,1719.8,2044.8,2169.5,2583.8,2835.1,2957.1,3203.6.
Methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is carried out the infrared absorption test condition is:
5, thermogravimetric differential thermal (TG-DTG) analytic curve (as shown in Figure 5) of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak: 179.2 ℃, and 262.8 ℃; The corresponding weightlessness of TG curve is 14.36%, 37.90%.
Methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is carried out thermogravimetric differential thermal (TG-DTG) analysis condition is:
Reference
1, Chinese patent, publication No. CN101863917A.
Claims (8)
1. the polymorphic of a methocarbamol di(2-ethylhexyl)phosphate sylvite, be referred to as crystal form P, and the X-ray powder diffraction collection of illustrative plates of described methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak:
2. polymorphic as claimed in claim 1, is characterized in that, the proton nmr spectra of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak,
1HNMR (400MHz, D
2O): δ=3.75 (s, 3H), 4.08-4.24 (m, 4H), 4.38-4.48 (m, 1H), 6.87-7.08 (m, 4H); Carbon-13 nmr spectra has following peak,
13CNMR (400MHz, D
2O): δ=55.68,64.44,68.11,69.65,112.44,113.89,121.57,121.96,147.43,148.40,159.25; Nucleus magnetic resonance phosphorus spectrum has following peak,
31PNMR (400MHz, D
2O): δ=0.47.
3. polymorphic as claimed in claim 1, is characterized in that, the mass spectrometry results of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is ,+c ESI:m/z=398 (M+1), m/z=436 (M+39);-c ESI:m/z=320,641.
4. polymorphic as claimed in claim 1, be characterised in that, the absorption peak wave number corresponding to infrared spectra of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P is with cm
-1Expression is respectively: 422.1,440.6,478.1,519.0,535.5,551.8,580.1,614.7,683.4,738.6,757.4,836.3,885.1,906.8,977.7,1024.9,1056.5,1078.1,1114.9,1142.7,1226.1,1255.4,1350.0,1367.3,1381.0,1410.7,1453.7,1508.3,1595.4,1719.8,2044.8,2169.5,2583.8,2835.1,2957.1,3203.6.
5. polymorphic as claimed in claim 1, be characterised in that, thermogravimetric differential thermal (TG-DTG) analytic curve of methocarbamol di(2-ethylhexyl)phosphate sylvite crystal form P has following peak: 179.2 ℃, and 262.8 ℃; The corresponding weightlessness of TG curve is 14.36%, 37.90%.
6. polymorphous preparation method of methocarbamol di(2-ethylhexyl)phosphate sylvite claimed in claim 1, it is characterized in that, with methocarbamol di(2-ethylhexyl)phosphate sylvite in water-soluble or mixed solvent, be heated to be chilled to normal temperature after dissolving fully more than 50 ℃, add poor solvent that crystal is separated out, obtain crystal form P at 50 ℃ of dry 8h after filtering.
7. method as claimed in claim 6, it is characterized in that, described mixed solvent refers to: the mixed solvent of a kind of composition in water and alcohol, ketone, ether, acid amides or sulfoxide type solvent, the mixed solvent of a kind of composition in water and methyl alcohol, ethanol, Virahol, acetonitrile, acetone, DMF, tetrahydrofuran (THF) or methyl-sulphoxide specifically.
Described poor solvent all refers to if no special instructions: alcohol, ketone, ether, acid amides or sulfoxide type solvent, specifically a kind of in methyl alcohol, ethanol, Virahol, acetonitrile, acetone, DMF, tetrahydrofuran (THF) or methyl-sulphoxide.
8. polymorphous application of methocarbamol di(2-ethylhexyl)phosphate sylvite claimed in claim 1 is for the preparation of the medicine for the treatment of muscle sprain, lumbar muscle strain or sciatica.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106349112A (en) * | 2016-08-24 | 2017-01-25 | 浙江海洲制药有限公司 | Preparation method of methocarbamol beta isomer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1528058A1 (en) * | 1999-12-08 | 2005-05-04 | Pharmacia Corporation | Polymorphic crystalline forms of celecoxib |
| CN1823741A (en) * | 2005-12-28 | 2006-08-30 | 严洁 | Methocarbamol dry mixing suspension |
| CN1843343A (en) * | 2006-02-16 | 2006-10-11 | 严洁 | Methocarbamol dispersion tablet |
| CN101863917A (en) * | 2010-06-17 | 2010-10-20 | 天津市若围药物研究所 | Methocarbamol salt |
-
2013
- 2013-03-22 CN CN2013100950423A patent/CN103130684A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1528058A1 (en) * | 1999-12-08 | 2005-05-04 | Pharmacia Corporation | Polymorphic crystalline forms of celecoxib |
| CN1823741A (en) * | 2005-12-28 | 2006-08-30 | 严洁 | Methocarbamol dry mixing suspension |
| CN1843343A (en) * | 2006-02-16 | 2006-10-11 | 严洁 | Methocarbamol dispersion tablet |
| CN101863917A (en) * | 2010-06-17 | 2010-10-20 | 天津市若围药物研究所 | Methocarbamol salt |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106349112A (en) * | 2016-08-24 | 2017-01-25 | 浙江海洲制药有限公司 | Preparation method of methocarbamol beta isomer |
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